Project description:Mapping of expression quantitative trait loci (eQTL) is a powerful means for elucidating the genetic architecture of gene regulation. Yet, eQTL mapping has not been applied towards investigating the regulation architecture of genes involved in the process of population divergence, ultimately leading to speciation events. Here, we conducted an eQTL mapping experiment to compare the genetic architecture of transcript regulation in adaptive traits differentiating the recently evolved limnetic (dwarf) and benthic (normal) species pairs of lake whitefish. The eQTL were mapped in three data sets derived from a F1 hybrid-dwarf backcrossed family: the entire set of 66 genotyped individuals, and the two sexes treated separately. We identified strikingly more eQTL in the female dataset (174), compared to both male (54) and combined (33) data sets. The majority of these genes were not differentially expressed between male and female progeny of the backcross family, thus providing evidence for a strong pleiotropic sex-linked effect in transcriptomic regulation. The subtelomeric region of a linkage group segregating in females encompassed more than 50% of all eQTL, which exhibited the most pronounced additive effects. We also conducted a direct comparison of transcriptomic profiles between pure dwarf and normal progeny reared in controlled conditions. We detected 34 differentially expressed transcripts associated with eQTL segregating only in sex-specific data-sets, and mostly belonging to functional groups that differentiate dwarf and normal whitefish in natural populations. Therefore, these eQTL are not related to inter-individual variation, but instead to the adaptive and historical genetic divergence between dwarf and normal whitefish. This study exemplifies how the integration of genetic and transcriptomic data offers a strong means for dissecting the functional genomic response to selection by separating mapping family specific effects from genetic factors under selection, potentially involved in the phenotypic divergence of natural populations. Keywords: eQTL mapping
Project description:Kernel development is accompanied by complex gene networks. Expression quantitative trait loci (eQTL) analysis is an efficient way to detect the regulatory elements of genes, especially the trans-eQTLs help to construct the regulatory networks of genes and contribute to a better understanding of the intrinsic mechanisms of biological processes. Till now, the 15 DAP (day after pollination) eQTL has been elucidated in maize kernel, but little is known about the early stage. Here, we conduct eQTL analysis for 5 DAP maize kernel using 318 maize inbred lines. The results will provide insights into the genetic basis of early kernel development.
Project description:The coat color of mammals is determined by the melanogenesis pathway, which is responsible for maintaining the balance between black-brown eumelanin and yellow-reddish phaeomelanin. It is also believed that the color of the bovine nose is regulated in a similar manner; however, the molecular mechanism underlying pigment deposition in the black nose has yet to be elucidated. The aim of the present study was to identify melanogenesis-associated genes that are differentially expressed in the black vs. yellow nose of native Korean cows. Experiment, Yellow nose vs. Black nose HanWoo
Project description:The coat color of mammals is determined by the melanogenesis pathway, which is responsible for maintaining the balance between black-brown eumelanin and yellow-reddish phaeomelanin. It is also believed that the color of the bovine nose is regulated in a similar manner; however, the molecular mechanism underlying pigment deposition in the black nose has yet to be elucidated. The aim of the present study was to identify melanogenesis-associated genes that are differentially expressed in the black vs. yellow nose of native Korean cows.
Project description:In this study we use RNAseq to explore allele specific expression (ASE) in adipose tissue of male and female F1 mice, produced from reciprocal crosses of C57BL/6J and DBA/2J strains. Comparison of the identified cis-eQTLs, to local-eQTLs, that were obtained from adipose tissue expression in two previous population based studies in our laboratory, yields poor overlap between the two mapping approaches, while both local-eQTL studies show highly concordant results. Specifically, local-eQTL studies show ~60% overlap between themselves, while only 15-20% of local-eQTLs are identified as cis by ASE, and less than 50% of ASE genes are recovered in local-eQTL studies. Utilizing recently published ENCODE data, we also find that ASE genes show significant bias for SNPs prevalence in DNase I hypersensitive sites that is ASE direction specific. We suggest a new approach to analysis of allele specific expression that is more sensitive and accurate than the commonly used fisher or chi-square statistics. Our analysis indicates that technical differences between the cis and local-eQTL approaches, such as differences in genomic background or sex specificity, account for relatively small fraction of the discrepancy. Therefore, we suggest that the differences between two eQTL mapping approaches may facilitate sorting of SNP-eQTL interactions into true cis and trans, and that a considerable portion of local-eQTL may actually represent trans interactions.
Project description:Prostate cancer cell lines are particularly racially and clinically homogenous, and while there has been significant work in the development of additional models, few have been created without oncogenic transformation. Here we describe the derivation of a spontaneously immortalized primary prostate cancer cell line from a Black Caribbean patient with Gleason 7 prostate cancer – designated CaB34 - which presents a novel model for pre-clinical study of localized prostate cancer. From CaB34, a paired radioresistant subline CaB34-CF was generated using a clinically relevant fractionated radiotherapy schedule. Both CaB34 and CaB34-CF express prostate-specific markers including CK18, NKX3.1, and AMACR. Multi-omic analyses using RNAseq and shotgun proteomics identified NNMT as the most significantly dysregulated target in CaB34-CF. Bioinformatic analysis determined that NNMT was more abundant within prostate tumors compared to benign prostate, supporting a role in tumor progression. Knockdown studies of NNMT demonstrated significant radiosensitization of both CaB34-CF cells, which was largely a result of increased radiation-induced cellular senescence. Our findings present NNMT as a potential therapeutic target for sensitization of radioresistant disease. Together, our research provides a paired model of treatment naive and radioresistant disease to address mechanisms of therapy resistance, while expanding the racial diversity of prostate cancer cell lines for the research community.